The overall objective of our research is to understand the mechanisms involved in the regulation of mRNA metabolism in eukaryotes. We have been concentrating on the chick oviduct system where steroid hormones are involved in the regulation of egg white protein mRNA synthesis and degradation. We have developed an in vitro culture system that responds to steroids (estrogen, progesterone and glucocorticoids) in a manner that is quantitatively and qualitatively similar to the intact animal. This system will be used to study the nuclear events that lead to the activation of transcription of ovalbumin and conalbumin mRNA. We also intend to study the effects of steroids on mRNA stability using pulse-chase techniques. The long-range goal is to establish a cell-free transcription system that responds to steroid hormones. More recently we have begun studying the regulation of metallothionein mRNA production in mouse liver. This small protein is induced in the liver in response to glucocorticoids and heavy metals. We intend to clone this gene and then study the regulation of metallothionein mRNA synthesis and degradation in cultured liver cells. We will also begin selecting for cadmium resistants mutants for future analysis.